Highly active vitamin preparation thoroughly freed from inactive ingredients.



" UNITED STATES PATENT oniuon;

ALFONS G-AMS BERTHOLIJ SCHREIBEB, F BASEL, SWITZERLAND, ASSIG-NORS TOSOCIETY OF CHEMICAL INDUSTRY IN BASLE, BASEL, SWITZERLAND.

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No Drawing.

To all whom it may concern:

Be it known that we, Dr. ALroNs GAMs,

a citizen of the Swiss Republic, and resident of Basel, Switzerland, andDr. BERTHOLD: 'SoHR IBER, a subject of the King of Hungary, and residentof Basel, Switzerland, have invented new Highly Active VitaminPreparations Thoroughly Freed From Inactive Ingredients, of whichthefollowing is a full,.clear, and exact specification.

It is known that most of the food products for human and animal use andother substances of vegetable and animal origin contain more or less ofthe so-called vitamins which are of importance in the economy of thehuman and animal life and are very useful to combat the so-calledavitaminous complaints as for instance beri-beri, scurvy, polyneuritis,pellagra, rickets and other morbid conditions due to malnutrition.Nobody succeeded heretofore in isolating these bodies in a formconvenient for therapeutical purposes and with a technicallysatisfactory yield.

. We have now found that highly active vitamin preparations, which areable to be employed for therapeutical purposes and are freed frominactive ingredients, are obtained by extracting food products or othersubstances of vegetable or animal origin, as for instance rice-bran,yeast, flesh, beans, etc., with dilute alcohol, separating the resulting aqueous alcoholic extracts from alcoholby distillation in avacuum and treating the aqueous extracts thus obtained successively inan acid state bylead acetate (sugar of lead) and in a neutral state bybasic lead acetate. Hereby the treatment with lead acetate (sugar oflead) in an acid state produces only the precipitationof the most of theinactive ingredients, the active substance remaining in solution. By thesubsequent treatment with basic lead acetate in a neutral solution,contrary to the statements in the literature of the subject, onlyfurther impurities are precipitated, without appreciable loss of activesubstances. The lead is separated according to known processes from thesolutions freed from the precipitated inactive ingredients and byevaporating the solutions thus obtained in a vacuum, directly a highlyactive preparation is obtained,

Specification of Letters Patent. P t t July 31-, 19 7, Application filedFebruary 2, 1917. Serial No. 146,256.

action, also easily soluble in absolute methylalcohol and insoluble inabsolute ethylalcohol, ether and acetone. By adding alkalin to itsaqueous solutions, the coloration of these latter turns to yellow and astrong methylamin smell is developed. By adding diazobenzene sulfonicacid to its solutions in an aqueous solution of sodium carbonate thecoloration of the said solutions turns to an intense Bordeaux-red. Withtannin, silver nitrate, phosphotungstic acid and phosphor-molybdic acidits aqueous solutions give precipitates;' the precipitate obtained withphosphotungstic acid dissolves on ad-. dition of a solution of sodiumcarbonate to a green to blue solution.

The food products or other substances of vegetable and animal originemployed as parent materials can,if desired, be subjected previously toa mechanical, or physical or chemical treatment making their extractionwith alcohol more easy, for instance a comminution with quartz sand, aplasmolysis', a hydrolysis with dilute acids or alkalis, a digestion forinstance with pepsin and hydrochloric acid, etc.

In order to obtain more concentrated vitamin preparations, which aresuificiently pure for injections, the active substances can beprecipitated from the solutions freed from most of the inactiveingredients and from lead by adding to the said solutions the usualalkaloid precipitants as for instance solutions of tannin,phosphotungstic. acid or heavy metal salts, whereafter the separatedprecipitates are decomposed in a liquid medium according to knownprocess and the solutions thus obtained evaporated to dry- Example 1':Rice bran in a broken up and finely divided, state is fully extracted,in the cold, with dilute alcohol and the solution obtained is freed fromalcohol by evaporating 'talline in a vacuum. The aqueous milky liquidis, if desired, separated by decantation from the oil and greasefloating on itssurface, hereafter it is acidified with acetic acid and asolution of lead acetate (sugar of lead) is added thereto until nofurther precipi tate is produced. Theclear solution, separated byfiltering oil the lead acetate precipitates, is accurately neutralizedand hereafter a neutralized solution of basic lead acetate is addedthereto until no further precipitate is produced. The solution separatedfrom the precipitate byfiltering is soluble in water toa'clearlsolutionand con- I parent material in'ia1concentrated,ihigh1ytains most of the vitamin, contained-in the active and permanentform., x 7

Example 2 Thefeebly solution thoroughly from the inactive Y ingredientsan to a p e i vacuum andfhereafter a sulfuric'solution of mercurybxid'isaddeduntilno further precipitate is produced. The precipitate isfiltered' off, washed and treated in an aqueous suspension.with'hydroge1i sulfid. After the liquid 5 hasf-been separated byfiltering fromymercury sulfid hydrogensulfid by evaporation-in ajfvacu,um or bonic acid and hereafter evaporated to dry-1 nessin a vacuum. Theremaining residue is a yellow-brown mass, .easily soluble in water,which contains the active substances of theparent material (vitamin)infa concentrated and very pure form.

Example 3: The solution active ingredientsand fromlead, obtainedaccording to Example 1, is acidified with oxalic acid and hereafter asolution of phosphotungstic acid is added thereto, until no furtherprecipitate is roduced. The precipitate separated by tering and washedout with water containing oxalic acid is suspended in water ,andtheoxalic acid in excess 1s precipitated wlth "calcium carbonate. Theprecipitate is filtered ofi and the filtrate is accurately freed fromcalcium hydroxid excess and evaporated to dryness in a vacuum. There isthus obtained a yellow-brown crystalline powder, easily soluble inwater, which contains the vitamin of the parent material employed in ahighly concentrated, very pure and permanent form, .and is suitable forpurposes of injecalcohol from from. the'-1ead," obtained accordconcentrated in a it is freed from] ous by introducing. an excess ofcanvbasic lead acetate freed from in:

v messes tion. As compared with the rocess described in the U. S.Letters atent No. 1162908 dated December 7, 1915, according to which avitamin preparation is prepared by precipitating yeast extract withphosphotungstic acid, treating the obtained precipitate with acetone anddecomposing the product insoluble in acetone by means of lead acetate,the present process has the great advantage that it separates the activesub stances contained in the parent materials in far highercyields.

Instead of the rice-bran indicated in the example, other nutrientsubstances of foodstufis, as for instance yeast, flesh, milk, beans,etc., and other substances of vegetable or animal origin can beemployed.

What we claimis:

1. The described process for the manu' facture of highly active vitaminpreparations thoroughly freed from 'inactiveingredients, consisting inextracting organic food products with dilute alcohol, removing the vtheresulting aqueous alcoholic extracts by distillation in a vacuum andprecipitating the inactive ingredients from a the remaining aqueousextracts by treating the said extracts successively in an acid state bylead acetate (sugar of lead) and in a neutral state by basic leadacetate, freeing the thus purified extracts from lead and evaporatingthe same in a vacuum.

2. The described process for--the manufacture of highly active vitaminpreparations thoroughly freed from inactive ingredients, consisting inextractin organic food products with dilute alcoho, removing the alcoholfrom the resulting, aquevacuum, precipitating the inactive ingredientsfrom "the remaining aqueous extracts' by treating the said extractssuccessively in an acid state by lead acetate (sugar of lead) and in aneutral state by freeing the thus purified extracts from lea treatingthe same afterward with one of the usual alkaloid precipitants ofalkaloids, decomposing in a liquid medium the precipitates thus producedand evaporating the resulting solutions in a vacuum.

3.; As" new articles of manufacture, the herein described highlyactivevitamin preparations thoroughly freed from inactive ingredient's,constltuting yellow-brown hygroscopicsubstances, which are soluble inwater t solutionsshowing with litmusa feeble acid reaction, becomingyellow and developing a strong methylamin smell on addition of alkalisand forming on addition of tannin,

silver nitrate, phosphotungstic acid and phosphomolybdic acidprecipitates of which those furnished with phosphotungstic acid dissolveon addition of a solution of sodium carbonate to a green to bluesolution, disalcoholic extracts by distillationin. a

solving easily in absolute methyl alcohol and insoluble in absoluteethyl alcohol, ether and acetone, and di$olving in watery solutions ofsodium carbonate to solutions becoming intense Bordeaux-red on additionof diazobenzenesulfonic acid.

In witness whereof We have hereunto signed our names this 11th day ofJanuary 1917, in the presence of two subscribing witnesses.

DR. ALFONS GAMS.

DR. BERTHOLD SCHREIBER.

Witnesses:

CARL O. SPANIER, AMAND RITTEY.

